Lona Mody, MD, M.ScAssociate Professor, Division of Geriatric Medicine
University of MichiganAssociate Director, GRECC
VA Ann Arbor Healthcare Systems
Control of Multi-drug Resistant Organisms: Hospitals and Nursing Homes (RCHEs)
Outline
Emerging and resistant pathogens
MRSA
Evolving epidemiology (nasal and extra-nasal) and clinical relevance
Infection control and prevention measures
R-GNB
Epidemiology and clinical relevance
Cephalosporin and quinolone resistance
VRE
C. difficile
Approach to preventing MDROs in nursing homes (NHs)
Impact of Multi-drug resistant organisms (MDROs)
MDROs: one of the greatest healthcare challenge
Responsible for
over 12,000 deaths
3.5 billion dollars (in US)
Prevalence estimates show an increase in MDROs
New antibiotics Resistance
New antibiotics not the only solution, need effective infection prevention strategies
S. aureus: Epidemiology in Hospitals
Staphylococcus aureus:
Responsible for serious infectionsAsymptomatic carriage predisposes symptomatic infectionsAnterior nares primary site of S. aureus
carriage
20-50% of general population
80% bacteremia are due to similar strain from patients’
nares
S. aureus
carriage at other extra-nasal sites
Oropharyngeal carriage –
4-60%Skin carriage –
8-70%
Intestinal carriage –
18-100%Groin carriage –
0-22%
S. aureus: healthy volunteers
Asymptomatic Carriage, N =1500 (Mertz CID, 2007)
Nares Oroph N (%)
+ + 343 (23)
+ - 219 (15)
- + 245 (16)
- - 693 (46)
Evolution of MRSA & VRE
1940
penicillinFirst used
penicillinresistance
vancomycin
MRSA
methicillin
gentamycin resistance
1988-
VRE
VISA reported in Japan
VRSA
20101950 1960 1970 1980 1990 2000
12 VRSA cases reported to date
streptomycin Successful in vitroTransfer of vanA
to MRSA
MRSA
Emerged in acute care in 1960s
Staphylococcal infections due to MRSA
1974: 2%
1995: 22%
2004: 63%
Transmission
MRSA: Prevalence in NHs (RCHE)
Location Year No. Patients % Colonized Comment
St. Louis 1985 74 12 Nasal
LA 1987 170 6.0-7.3 Nasal & wound
Pittsburgh VA-ECC
1986 432 13 Nasal
Vancouver 1989 120 34 Nasal & wound
Ann Arbor(VA-ECC)
1990 120 23 Nasal & wound
Ann Arbor(VA-ECC, Co NH)
2000-1 427 17 Nasal & wound
MRSA: extra-nasal colonization
Oropharyngeal colonization, 150 ICU
patients,
Harbath S (Switzerland) 2007, J Clin Microb
Nares Oro-pharynx N (%)
- - 137 (91.3)
+ + 7 (4.7)
+ - 5 (3.3)
- + 1 (0.7)
MRSA: extra-nasal colonization
266 MRSA in-patients
Ringberg H (Sweden); Scand J Infect Dis 2006;38:888-93
Nares Oroph Perineum Skin lesion
N (%)
+ - - - 45 (17)- + - - 46 (17)- - + - 15 (6)- - - + 68 (26)
MRSA: Hospitalized older adults
10,089 in-patients, Canada
Simor A et al, Infect Control Hosp Epidemiol 2005;26:838-41
Site ≥
65 yrN=6613 (%)
18-64 yrsN=3476 (%)
Nares 2,919 (44) 1,219 (35)*
Groin 1,413 (21) 536 (15)*
Urine 633 (10) 219 (6)*
* P < 0.05
MRSA: Risk factors in NHs
Impaired functional status
Indwelling devices such as urinary catheters and feeding tubes
Prior hospitalization
Urinary incontinence
Prior antimicrobial usage
Wounds and pressure ulcers
MRSA: Role of Indwelling DevicesHypothesis: MRSA carriage (both nasal and extra-nasal) would be more frequent in
NH residents with indwelling devices compared with controls
Study Facilities: 14 community NHs in Southeast Michigan
Study Design: Cross-sectional microbial prevalence study
Study Population:
All residents with an indwelling device (urinary catheter, feeding tube or PICC)
Randomly selected controls
Clinical data:
Age, comorbidity and functional status
Samples obtained from
nares, oropharynx, groin, peri-anal, wounds (if present), skin around enteral feeding tubes (if present)
Mody L et al: J Am Geriatr Soc 2007; 55:1921-6
Methods: Molecular epidemiology
Microbiology
S. aureus
and MRSA identified using standard microbiologic
methods
MRSA sub-typing
Pulsed field gel electrophoresis (PFGE)
Multiplex PCR methods to determine
mecA gene, SCCmec
type I-V, Panton-Valentine leukocidin
(PVL) toxin gene
Results
250 eligible residents
125 with devices
125 randomly selected controls
213 enrolled (85%)
108 residents in control group
105 residents in device group
46 with urinary catheters only
48 with feeding tubes only
6 with both urinary catheters and feeding tubes
5 with PICC lines only
Clinical Characteristics
Device Group (N = 105)
Control Group (N=108)
P value
Mean Age 78 (74-79) 81 (79-83) 0.04*
Female 60% 67% 0.16
Functional Status#
26 (24, 27) 20 (18, 21) 0.001*
Co-morbidity Score‡
3.0 (2.5, 3.3) 2.5 (2.1, 2.7) 0.04*
# Functional Status measured using Lawton and Brody’s physical self maintenance scale
‡
Charlson’s co-morbidity index
•P < 0.05
S. aureus
and MRSA carriage
0102030405060708090
100
S. aureus MRSA
ControlDevice
OR: 2.6, p = 0.006*
OR: 2.0, p = 0.04*
* Adjusted for age, functional status and co-morbidities
%
Positive
S. aureus
carriage: Indwelling devices & no. of sites
0
20
40
60
80
100
Control Group Device Group
S. aureus 3-6 sites
S. aureus 1-2 sites
S. aureus (-)% of patients
P < 0.001 for trend
N = 108 N = 105
MRSA carriage: Indwelling devices & no. of sites
0
20
40
60
80
100
Control Group Device Group
MRSA 3-6 sites
MRSA 1-2 sites
MRSA (-)% of patients
P < 0.001 for trend
N = 108 N = 105
Extra-nasal MRSA carriage
Device GroupN = 105% pos
Control GroupN = 108% pos
OR(95% CI)
P value
Any site 52 29 2.0 (1.1,3.8) 0.04
Nares 31 21 1.8 (0.9,3.5) 0.09
Oropharynx 26 11 2.7 (1.3,5.8) 0.006
Groin 25 5 6.8 (2.4, 19.3) < 0.001
Peri-anal 27 6 5.4 (2.1, 13.5) < 0.001
MRSA in RCHEs: Functional Status
Ann Arbor VA ECC, N = 341-
Bradley SF et al, Annals Intern Med 1991;115:417-22.
Functional Status TotalN
MRSAN (%)
I (min assist) 90 19 (21)
II (mod assist) 162 57 (35)
III (max assist) 84 41 (49)
MRSA in NHs (RCHE): Other risk factors
NHs in Leeds, UK; N = 715; Nares culture, Barr B, ICHE 2007;28:853-9
Proportion (%) with MRSA
P value Crude OR Adjusted OR
GenderFemaleMale
116/574 (20)43/141 (30) 0.008 1.8 (1.2,2.8) 1.6 (1.03,2.6)
Presence of deviceNoYes
141/673 (21)16/35 (38) 0.002 3.2 (1.5,6.6) 2.7 (1.3,5.7)
Use of antibioticsNoYes
141/657 (22)16/51 (31) 0.13 1.7 (0.9,3.4) NS
Presence of woundNoYes
146/679 (22)11/29 (38) 0.13 1.9 (0.8,4.5) NS
MRSA in RCHEs: Other risk factors
NHs in Germany; N = 3,236; Nares culture
von Baum, Infect Control Hosp Epid 2002;23:511-15
% with MRSAN = 36
% without MRSA, N = 3200
P value
ORa
Male 32% 26% NS
Use of Antibiotics 23% 8% 0.006 1.6 (0.7,3.8)
Presence of wound 19% 4% 0.001 3.3 (1.3,8.0)
Urinary catheter 36% 9.6% 0.001 2.7 (1.2,6.3)
Feeding Tube 19.4% 9.3% 0.002 1.5 (0.6,4.1)
MRSA: Evolving Epidemiology
MRSA in 20th
century
Acute care 1960s
Spill over to NHs in 1980s
Healthcare exposure a pre-requisite
MRSA in 21st
century
Can be healthcare associated or community-associated
Community-associated seen in schools, athletes, jails, overcrowding
Spill over to hospitals
MRSA: Healthcare vs. CommunityHealthcare associated MRSA (HA-MRSA)
Community associated MRSA (CA-MRSA)
Healthcare exposure; Dialysis, indwelling devices, NH residents
No healthcare exposure; Athletes, prisoners, young children, military recruits
Nasal Nasal & extra-nasal, evolving
Surgical wound infections, UTI, nosocomial pneumonia, blood stream
Boils, spider bites, pneumonia, septicemia
SCCmec type II, PVL (-) SCCmec type IV, PVL (+)
Resistant to majority of antibiotics Susceptible to several antibiotics
MRSA in NHs: Emergence of CA-MRSA?
Finland:
6.6% of 76 residents with CA-MRSA
Kerttula A, J Clin Microbiol 2005;43:6161-3
Germany:
7.6% of 197 residents with CA-MRSA
Raab U, Infect Control Hosp Epidemiol 2006;27:208-11
Hong Kong:
13 NHs
2.4% of 949 residents CA-MRSA
Ho PL, Infect Control Hosp Epidemiol 2007;28:671-8.
CA-MRSA in MI NHs
PCR Device Group (N=55) Control Group (n=31)
SCCmec type
II (HA-MRSA) 47 26
IV (CA-MRSA) 5 3
Unknown 2 1
PVL (+) 1 1
Mody L et al, Clin Infect Dis 2008-, in press
MRSA: Natural history in NHs
Transfers from acute care
2-25% of new residents colonized
Persist and spread
Enclosed environment, poor functional status, presence of devices
HCW to resident and resident to resident spread
Serial studies show persistence
MRSA in NH (RCHEs): Persist and Spread
Prolonged colonization,N=22
Persistent colonization with original strain/s, N = 13
Persistent colonization with original strain; transient colonization with new strain/s, N = 5
Acquisition of a new strain that persists, N = 4
MSSA, N = 9
MRSA, N = 4
MRSA, N = 5
MRSA, N = 3
MSSA, N = 1
New strain, MSSA, N = 3
New strain, MRSA, N = 1
Transient strain, MRSA, N = 4
Transient strain, MSSA, N = 1
MRSA persistence
Mody et al ICHE 2006; 27:212-4
MRSA Infections
3-25% of MRSA carriers develop infections
Skin & soft tissue, urinary tract infections, respiratory infections
Atypical presentation
MRSA not the only MDRO…
MRSA VRE MDRGN C. difficile
Pagers Stethoscopes Bedrails Bed frames
White coats Sinks
Blood pressure cuffs Ventilator water
Computer keyboards
Environmental sampling
Adapted from: Hebert and Weber, Infection Prevention and Control in the Hospital, 2011
MRSA from environmental cultures
Quinolone Resistance
Frequent use to treat NH infections
Resistance in GNB
E. coli: 5-41%
P. aeruginosa: 27- 67%
K. pneumoniae: 7-14%
P. mirabilis:
38-57%
Viray M, Infect Control Hosp Epidemiol 2005;26:56-62
Bonomo R, Clin Infect Dis, 2000;31:1414-22
Antibiotic pressure
-lactam resistance in GNBs
GNB carry extended spectrum -lactamases (ESBLs)
Outbreaks:
Massachusetts Chronic Care Facility: 1990
25 patients over 4 months
Ceftazidime use
Chicago: 1992
55 hospitalized patients with CTZ-R
31/55 from 8 NHs with CTZ-R
Point prevalence study in 1 NH: 18/39 CTZ-R GNB
Bonomo R, Clin Infect Dis, 2000;31:1414-22
Resistant GNB: VA ECC experience
Ann Arbor Portland Pittsburgh
Ceftriaxone -R 27/286 (9.4%) 26/311 (8.4%) 5/754 (0.7%)
Ceftazidime- R 33/349 (9.5%) 7/121 (5.8%) 20/876 (2.3%)
Mody L et al Infect Control Hosp Epidemiol; 2001
Indwelling Devices: R-GNBOutcome
Devices
Controls
ORa
P-value
% (+)
% (+)
MRSA
55
29
2.0
.04*(1.01,3.8)
VRE
9
9 1.1 .88
CTZ-R GNB
24
5
5.6 .003*(1.8,17.0)
* Adjusted for age, co-morbidities and functional status
Risk Factors for R-GNB
Indwelling devices
Poor functional status
Pressure ulcers/wounds
Quinolone use
Prior hospitalization
VRE (Vancomycin Resistant Enterococci)
VRE a relatively recent discovery
But widespread, esp. in hospitals with significant mortality and
morbidity
VRE accounts for ~ 30% of ICU isolates of Enterococcus
in the United States
NHs (RCHE)
Prevalence varies from 5-20%
Commonality of risk factors: MRSA, R-GNB, C. difficile
Use of indwelling devices
Prior hospitalization
Functional impairment
Prior antimicrobial usage
Presence of wounds
Infection Control Strategies in NHs
Progress in LCTFs infection control
Guidelines from various national societies
Immense variations in practice
Do-nothing to do-everything
No controlled trials
Issues to remember
NHs are not hospitals
Rehab and socialization critical
Screening cultures require infrastructure
NHs may not want to or need to know their MRSA status (although this is changing)
Infection Control Strategies: MRSA
Hand Hygiene
Active Surveillance
Nares or multi-site
All residents or high risk residents such as new admits or those
with indwelling
devices
Mupirocin
Effective in eradicating for up to 6 months
(Mody, Kauffman, Bradley et al Clin Infect Dis 2003;37:1467-74)
Re-colonization risk
Mupirocin resistance a concern
Reduction in infections needs to be established
Chlorhexidine baths
Some data in acute care, no studies in NHs
Hand Hygiene Products
Good Better Best
Plain Soap Antimicrobial soap
Alcohol-based handrub
Hand Hygiene adherence
1. Gould D, J Hosp Infect 1994;28:15-30. 2. Larson E, J Hosp Infect 1995;30:88-106. 3. Slaughter S, Ann Intern Med 1996;3:360-365. 4. Watanakunakorn C, Infect Control Hosp Epidemiol 1998;19:858-860. 5. Pittet D, Lancet 2000:356;1307-1312.
Year of Study
Adherence Rate
Hospital Area
1994 (1)
29%
General and ICU
1995 (2)
41%
General
1996 (3)
41%
ICU
1998 (4)
30%
General
2000 (5)
48%
General
Hand cleansing in NHs
Thompson et al, MMWR 1993;42:672-75
Hand cleansing
32% before interaction
64% after interaction
Glove usage
84% compliance
Changed only 15% of times
Hand cleansing in NHs
What do healthcare workers carry on their hands?Does alcohol gel reduce these pathogens?Does alcohol gel increase hand hygiene compliance?
Mody L et al Infect Control Hosp Epidemiol; 2003:24:165-171
Study Methods
Quasi-experimental study
Two 36-bed wards
Cultured hands of healthcare workers
Baseline
After an educational intervention
After introducing alcohol gel on intervention ward
Standard microbiologic tests to identify
S. aureus,
Gram-negative pathogens
Yeast, VRE
DemographicsWard A Ward B
(GEL) (Soap & Water)
No. of HCWs
23
23
F:M
23:0
21:2
RN:Nursing Aide
6:17
7:16
Nail Polish
4 3
Artificial Nails
5 3
HCWs Hands: What do they grow?
Organism
N (%)
GNB
30 (65)Yeasts
18 (39)
S. aureus
9 (20)VRE
4 (9)
Efficacy of Soap vs GEL in eliminating pathogens from the hands of HCW
0
20
40
60
80
100
Eff
icac
y (%
)
GNB SA Yeasts
GELSoap
p=.03
p=.003p=.07
Effect of an educational intervention & introduction of GEL on hand cleansing frequency
02468
10121416
Baseline Post-education
Post-intervention
Intervention WardControl Ward
p = .04
Han
dcle
ansi
ng ti
mes
/hr
Oro-pharyngeal Decolonization
Cardiothoracic Surgery
Does peri-operative decontamination lead to reduced infections?
991 patients randomized to Chlorhexidine Gluconate or placebo
Nosocomial infection rate: 19.8% in Rx group; 26.2% in placebo group
NNT: 16 patients needed to be treated to prevent 1 infection
Documented significant reduction in S. aureus
Segers P et al JAMA 2006;296:2460-6
Infection Control Strategies: MRSA
Hand Hygiene
Active Surveillance
Nares or multi-site
All residents or high risk residents such as new admits or those
with
indwelling devices
Mupirocin
Effective in eradicating for up to 6 months
Mody L, Kauffman CA, Bradley SF et al CID 2003
Re-colonization risk
Reduction in infections needs to be established
Chlorhexidine baths
Some data in acute care, no studies in NHs
Infection Control: Other MDROs
Control of transmission
Preventing the spread of resistant organisms principally via the
hands of healthcare workers
Transient vs. Resident flora on hands
Preventing environmental contamination
Antibiotic Stewardship
Hand Hygiene
VRE:
Can easily pass on HCW hands and contaminate environment
Documented on 13-41% of HCWs
Can persist for up to an hour
Can be successfully removed with soap and water or alcohol based
hand rub
R-GNB
Commonly found on environmental surfaces as well as HCW hands
Survive longer on inanimate objects than hands
Artificial finger nails a risk factor
Hand hygiene adherence shown to reduce MDR colonization
C. difficile
form spores
Isolated from environment; survives for prolonged period
Antiseptic hand rubs may not be as effective
Physical removal of spores by soap and water required
Bleach cleaning for environment
Isolation precautions and PPE
Isolation precautions one of the oldest form of infection control
Modern medicine moving away from strict isolation to use of personal protective equipment (PPE)
Gloves: reduces risk of hand contamination
VRE: current guidelines recommend isolation
few well designed studies; significant circumstantial evidence in favor of using gowns and gloves to prevent transmission
Gown free period shown to increase transmission
R-GNB
Few studies to support active surveillance and isolation
Some data supporting the use of gowns and gloves in reducing transmission
Well-designed studies lacking
C. difficile
If diarrhea, then contact precautions as well as gowns and glove
use
Several studies now support this approach
Challenges to Isolation Precautions in NHs
Can compromise quality of care
Concerns about reduce nurse and physician oversight
Potential for depression and anxiety especially in older adults
Active surveillance
MRSA
Targeted surveillance for MRSA useful in acute care setting
Routine surveillance in ICU with appropriate infection control measures, shown to be useful
Universal hospital surveillance can also reduce MRSA
VRE
A large proportion undetected by clinical cultures
Some evidence showing active surveillance can reduce VRE bacteremia
Can consider surveillance in high-risk patients
R-GNB
Active surveillance not well-studied
Heterogeneity of GNB a major challenge
Active surveillance can increase appropriate antibiotic usage, but research is lacking
C. difficile:
A significant proportion of asymptomatic carriage
Active surveillance generally not recommended
Challenges to Active Surveillance in NHs (RCHE)
At any given time:
30% colonized with MRSA
10-20% with VRE
35-40% with CIP-R GNB
Issues to consider
Is it practical to culture 1.5 million residents?
Can we define specific high risk groups?
Multi-anatomic site cultures? Nares alone may not suffice
How often should they be cultured?
Short-stay: 2-3 months; Long-stay: 3-4 yrs
If positive then…?
Antimicrobial Stewardship
Rational use of antibiotics critical
Balance between effective treatment and avoidance of resistance
Two major approaches:
Prospective auditing/feedback
Pre-authorization
Leads to effective therapy and cost savings
Computerized decision support emerging
Research in NHs lacking
Antimicrobial Stewardship: Limitations
Lack of research to demonstrate sustained decrease in overall burden of MDROs
Research lacking in NHs
Only antimicrobial stewardship without other infection control approaches may fail
Difficult to predict which antibiotic to restrict
Summary
Epidemiology of MRSA in NHs is evolving
more studies required
GNB resistance to quinolones and cephalosporins frequent
Goals of infection control in NHs different
Need for Infection prevention and MDRO transmission research in NHs
